Structural fragility analysis of Andes hantavirus pathogenesis identifies three weakly coupled drug-targetable modules: a network topology-guided tritherapy hypothesis

Structural fragility analysis of a 45-protein, 53-interaction Andes virus (ANDV) pathogenesis network using the TCGE framework reveals a Fragility Index of 77.4% (hyper-fragile). Three weakly coupled pathological modules converge on lethal pulmonary oedema: (1) VEGF/VEGFR2-mediated vascular leakage, (2) mTOR-driven lymphatic endothelial dysfunction, (3) NF-κB-driven cytokine storm. Each module maps to always-fragile edges targetable by already-approved drugs (bevacizumab, rapamycin, tocilizumab). Structural hypothesis for preclinical evaluation — not a clinical recommendation. Published in response to the ongoing MV Hondius outbreak (35 cases, 14 countries, 3 deaths as of May 2026).